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Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2023)

The roles of dietary antigen-specific IgG are understudied as compared to IgE-mediated responses. Leviatan et al (Immunity 2022 ;55:2454-69.e6; https://doi.org/10.1016/j.immuni.2022.11.004) utilized phage display technology to assess IgG responses against a comprehensive library of food peptides in a population cohort of over 1,000 nonallergic subjects. A vast array of food antigens, including from both plant and animal sources, induced systemic IgG responses across wide swaths of the population. Importantly, anti-food IgG responses correlated with dietary intake and were stable over a span of 5 years. These findings provide a reference map of the immunogenic epitopes of food antigens bound by IgG and may inform future study into the contributions of food antigen-directed IgG responses to health and disease. We asked corresponding author Thomas Vogl, PhD, of the Medical University of Vienna, Wien, Austria, to comment on the study. He writes, “While it has been appreciated that also nonallergic individuals produce antibodies against dietary antigens, the abundance and specificity of such responses were incompletely characterized. We have now profiled antibody binding against more than 20,000 peptides of food proteins, mapping population-wide repertoires in 1,000 nonallergic individuals, which will also be relevant for allergy testing.” By utilizing single-cell transcriptomic profiling of murine eosinophils, Gurtner et al (Nature 2022 Dec 12; https://doi.org/10.1038/s41586-022-05628-7) identified 2 distinct intestine-resident eosinophil subsets (termed active and basal) with marked differences in gene expression, surface protein expression, and localization within the intestine. Notably, basal eosinophils exhibited enhanced expression of genes involved in tissue remodeling. Active eosinophils exerted a protective role during colonic inflammation with both antibacterial and immune regulatory functions. Through genome-wide CRISPR screens and functional assays, the authors identified that IL-33 promoted active eosinophil maturation whereas IFN-γ potentiated their regulatory function during colitis. Finally, active eosinophils co-localized with CD4+ T cells and were enriched in colonic tissue obtained from human patients with inflammatory bowel disease. In total, these results identify a novel immunoregulatory subset of intestine-resident eosinophils.Active eosinophils exerted a protective role during colonic inflammation Active eosinophils exerted a protective role during colonic inflammation Gut food-specific IgA responses within the gut are classically thought to decrease IgE-mediated food allergies. However, a new study by Liu et al (Sci Transl Med 2022;14:eabq0599; https://doi.org/10.1126/scitranslmed.abq0599) has called this paradigm into question. After identifying peanut-specific IgA in stool samples from nonallergic infants, they assessed for any relation between peanut-specific IgA levels and tolerance in a separate cohort of over 400 atopic children. Peanut-specific IgA levels in stool did not associate with protection against future peanut allergy. In fact, higher plasma peanut-specific IgA was observed in the presence of peanut allergy. Notably, these findings were generalizable to other dietary antigens as similar results were identified with egg white-specific IgA and egg allergy. These findings challenge the notion of a tolerogenic role for food-specific IgA in the natural history of food allergy.Elise Liu and Stephanie EisenbarthView Large Image Figure ViewerDownload Hi-res image Download (PPT) We asked first author, Elise Liu, MD, PhD, of Yale University, New Haven, Connecticut, and last author, Stephanie Eisenbarth, MD, PhD, of Northwestern University, Chicago, Illinois, to comment on the study. They write, “These data from patients enrolled in the GMAP, CoFAR2, POISED, and Twins studies show that higher levels of food-specific IgA do not correlate with protection from developing, or likelihood to outgrow food allergy, nor does it corelate with the outcome of an oral food challenge. Because gut IgA is made to a wide variety of foods by almost every person tested, we believe it serves an important biologic function that still needs to be elucidated.” Respiratory syncytial virus (RSV) imposes a large morbidity and mortality burden worldwide in young children, and novel preventive strategies including maternal vaccination and novel passive immunization therapies are in advanced stages of clinical development. Wildenbeest et al (Lancet Respir Med 2022 Nov 10;S2213-2600(22)00414-3; https://doi.org/10.1016/S2213-2600(22)00414-3) performed a birth cohort study (RESCEU) involving almost 10,000 participants from 5 European countries to clarify the health burden in the European Union. The incidence of RSV-related hospitalizations within the first year of life was 1.8% and comprised nearly half of all hospitalizations for respiratory tract infection. Notably, the majority of RSV-related hospitalizations occurred within the first 3 months of life. These results will likely inform future development of effective widespread RSV prevention programs. We asked corresponding author Louis Bont, MD, PhD, from the Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands, to comment on the study. He writes, “For the first time we know the tremendous burden of RSV in healthy babies in our part of the world. Unfortunately, the burden in developing countries is even much higher.” Due to significant heterogeneity of treatment responses to dupilumab in patients with atopic dermatitis, Spekhorst et al (JAMA Dermatol 2022;158: 1409-13; https://doi.org/10.1001/jamadermatol.2022.4639) performed a prospective observational cohort study involving almost 300 subjects to examine the predictive value of serum dupilumab levels on treatment response and risk of adverse events. No association was observed between serum dupilumab levels after 16 weeks of treatment and either responder status or adverse effects. Furthermore, serum dupilumab levels did not predict response during the first year of treatment. Collectively, these findings do not support a role for using serum dupilumab levels to optimize atopic dermatitis treatment.Serum dupilumab levels did not predict responseNews items were written by medical writer Jared Travers, MD, PhD. Serum dupilumab levels did not predict response News items were written by medical writer Jared Travers, MD, PhD.